Chasing after the causes of platelet disorders
George Corcoran, MD, and
Kandice Kottke-Marchant, MD, PhD
The following article was adapted from the Archives of Pathology
& Laboratory Medicine (2002;126:133-146).
exist for platelet-derived bleeding disorders. The laboratory evaluation
of these disorders can range from simple to complex and should initially
include a thorough evaluation of the patient's medical history,
concentrating on personal and familial bleeding disorders and current
medications. With this as a starting point, the algorithms presented
here may be helpful in elucidating the underlying etiology for platelet-derived
Role of platelets in hemostasis
Platelets are small (2 µm-diameter), non-nucleated blood cells
produced in the bone marrow from megakaryocytes. They are rapidly
activated by blood vessel injury and are a crucial component of
the primary hemostatic response. In their unactivated state, platelets
are roughly discoid in shape and contain cytoplasmic organelles,
cytoskeletal elements, invaginating open-canalicular membrane systems,
and platelet-specific granules called alpha and dense granules.
Platelets have numerous intrinsic glycoproteins attached to the
outer surface of their plasma membrane that are receptors for such
ligands as fibrinogen, collagen, thrombin, and thrombospondin to
von Willebrand factor and fibronectin.1
Platelets promote hemostasis by the following interconnected mechanisms:
- adhering to sites of vascular injury or artificial surfaces
- releasing compounds from their granules
- aggregating together to form a hemostatic platelet plug
- providing a procoagulant surface for activated coagulation protein
complexes on their phospholipid membranes (Fig.
Platelet adhesion to subendothelium is the initial step in platelet
activation. The subendothelium is composed of extracellular matrix
proteins, many of which are ligands for receptors on the platelet
surface. These adhesive proteins are exposed when the endothelial
layer is disrupted. Due to the large number of extracellular matrix
proteins and a high density of platelet surface receptors, platelets
adhere rapidly to areas of vascular injury. Von Willebrand factor,
a large, multimeric protein secreted into the extracellular matrix
from endothelial cells, facilitates platelet adhesion by binding
to platelet surface glycoprotein Ib/IX/V, especially at high shear
rates.2 Platelets can also adhere
to vascular wall-associated fibrin or fibrinogen by interacting
with platelet surface glycoprotein IIb/IIIa.3
After adhering to the subendothelium, platelets undergo cytoskeletal
activation, which leads to a change in their shape and the development
of pseudopods. Intracellular signaling processes leading to increased
cytoplasmic calcium then initiate a secretory release reaction that
releases products from the alpha granules (platelet factor 4, β-thromboglobulin,
thrombospondin, platelet-derived growth factor, fibrinogen, VWF)
and dense granules (adenosine diphosphate [ADP], serotonin).4
The release of ADP combined with calcium mobilization leads to a
conformational change of the fibrinogen receptor, the GP IIb/IIIa
receptor complex (integrin αIIbβ3).
This initiates the process of aggregation, in which a GP IIb/IIIa
receptor on one platelet is bound in a homotypic fashion to the
same receptor on adjacent platelets via a central fibrinogen molecular
bridge. Beside ADP, other agonists, such as epinephrine, thrombin,
collagen, and platelet-activating factor, can initiate platelet
aggregation by interacting with membrane receptors. This platelet-release
reaction and aggregation recruits many other platelets to the vessel
wall and forms a hemostatic platelet plug.
Activated platelets also play a vital procoagulant role that serves
as a link between platelet function and coagulation activation.
Platelet membrane phospholipids are rearranged during activation,
and phosphatidyl serine is transferred from the inner table to the
outer table of the platelet membrane, providing a binding site for
phospholipid-dependent coagulation complexes that activate factor
X and prothrombin.
Laboratory tests for evaluating platelet function
A thorough clinical and family bleeding history should be taken
and should include an assessment of the duration, pattern, and severity
of bleeding problems. Platelet-mediated bleeding disorders usually
will result in a mucocutaneous bleeding pattern. In contrast, coagulation
protein disorders typically will result in hemarthrosis and deep
tissue bleeding. A thorough history should rule out the consumption
of any food or drugs (prescription and over-the-counter) that may
alter platelet function.5 Systemic
diseases, including renal disease and hepatic malfunction, may also
be associated with platelet dysfunction.
Platelet count and peripheral blood smear
The reference range of the platelet count is between 150 and 400
x 103/µL of blood, although values
well below the lower limit may be adequate for hemostasis in most
clinical situations. Pseudothrombocytopenia should be considered
when a low platelet count is encountered. It commonly is caused
by cold-reacting platelet agglutinins and platelet-neutrophil binding
(platelet satellitism). Pseudothrombocytopenia can be diagnosed
by examining a peripheral smear where large aggregates of platelets
are observed, typically at the feathered edge. Giant platelets observed
with macrothrombocytopenia syndromes also may give erroneously low
The mean platelet volume is an indication of platelet size. Normal
MPV ranges are approximately 7 to 11 fL. The MPV can be an indication
of platelet turnover because younger platelets tend to be larger.
A spectrum of platelet sizes is seen in patients with rapid turnover,
while true congenital macrothrombocytopenias usually have uniformly
Initial platelet function tests or bleeding time
The bleeding time traditionally was the only platelet-function screening
test available.6 It involves creating
a standardized cut in the skin and measuring the time it takes for
the cut to stop bleeding. The BT result depends not only on platelet
number and function but also on fibrinogen concentration. This,
in combination with procedural variability, makes it difficult to
achieve an accurate BT. Newer automated whole blood platelet-function
screening assays, such as the Platelet Function Analyzer-100 (PFA-100,
Dade Behring), are being used to screen platelet function.
Bone marrow examination
Examining bone marrow may help in evaluating thrombocytopenia or
thrombocytosis. This may be helpful in ascertaining whether thrombocytosis
is due to reactive or myeloproliferative disorders. In the thrombocytopenic
patient, examining the bone marrow is useful in determining the
presence or absence of megakaryocytes; absence indicates dysfunctional
marrow and increased numbers suggest peripheral destruction.
Platelet aggregation studies measure the ability of agonists to
cause in vitro platelet activation and platelet-to-platelet binding.
These studies can be performed in whole blood using an impedance
technique or in platelet-rich plasma using a turbidimetric technique.7
Turbidimetric platelet aggregation is measured by the increase in
light transmission after adding an aggregation agonist such as ADP,
collagen, arachidonic acid, or epinephrine. Another important reagent
used in evaluating platelet function by aggregation is the antibiotic
ristocetin, which helps bind VWF to the glycoprotein Ib/IX/V complex.
Ristocetin-induced platelet aggregation is an assay that can detect
von Willebrand disease and some platelet dysfunctions, such as Bernard-Soulier
Coagulation testing and von Willebrand assay
The laboratory evaluation of platelet dysfunction should also include
the prothrombin time and activated partial thromboplastin time to
exclude coagulopathy as the reason for bleeding. Von Willebrand
disease is often considered in the differential diagnosis of bleeding
disorders with long bleeding times or abnormal platelet function
screening test results, but it is not strictly a disease of platelet
Electron microscopy may be used for the ultrastructural evaluation
of platelets, particularly in patients with suspected storage pool
disorders. In such patients, electron microscopy shows a decrease
or absence of the organelles that store adenine nucleotides, serotonin,
and calcium. Giant platelet disorders also have characteristic electron
Newer methods of platelet evaluation
Newer assay systems to assess platelet function are now available
and include the PFA-100, Ultegra (Accumetrics), and Plateletworks
The PFA-100 measures platelet-related primary hemostasis in citrated
whole blood specimens.9 It uses
two disposable cartridges that contain a membrane with a central
aperture (147 µm) coated with aggregation agonists (collagen and
epinephrine, and collagen and ADP), through which platelets are
passed at high shear rates (5,000 to 6,000 s-1).
The instrument measures the "closure time" required for platelets
to adhere to the membrane, aggregate, and occlude the aperture.
The collagen-epinephrine cartridge detects platelet dysfunction
induced by intrinsic platelet defects, von Willebrand disease, or
platelet-inhibiting agents. The collagen-ADP cartridge usually produces
abnormal results with platelet disorders and von Willebrand disease
but produces a normal closure time with aspirin-like drugs because
of their high ADP concentrations. Von Willebrand disease, intrinsic
platelet dysfunction, and nonaspirin drugs may produce an abnormal
closure time with both cartridges.
The rapid platelet-function assay Ultegra is an automated turbidimetric
whole blood assay designed to assess platelet aggregation based
on the ability of activated platelets to bind fibrinogen.10
Fibrinogen-coated polystyrene microparticles agglutinate in whole
blood in proportion to the number of available platelet glycoprotein
IIb/IIIa receptors.10 The Ultegra
specifically is designed to measure the effect of glycoprotein IIb/IIIa
antagonist drugs, such as abciximab, tirofiban, or eptifibatide.
It is not sensitive to such drugs as aspirin, clopidogrel, or ticlopidine,
and it is not designed to detect platelet function disorders or
von Willebrand disease.
Plateletwork's rapid platelet aggregometer is designed to determine
the percentage of platelet aggregation in fresh whole blood samples
taken during interventional cardiac procedures. It measures the
change in the platelet count due to aggregation of functional platelets
in the blood sample. It is the first bedside test to simultaneously
measure platelet count and platelet aggregation.
Flow cytometry has been used to study platelet structure and function,
but only in specialized centers. It detects platelet activation
using antibodies to proteins newly expressed on the platelet surface
during activation. Platelet flow cytometry can be used to diagnose
deficiencies of platelet surface glycoproteins. It also can be used
to measure platelets with increased RNA content using the dye thiazole
orange, which binds to RNA and DNA. This technique is used to evaluate
whether thrombocytopenia is due to increased platelet destruction
or decreased platelet production since newly released platelets
have increased RNA content.
Categories of platelet-derived bleeding diathesis
Platelet dysfunction can lead to a clinical bleeding disorder
that is congenital or acquired in nature. Laboratory evaluation
of platelet dysfunction is often complex, but it can be simplified
by using a diagnostic algorithm and classifying such disorders as
platelet dysfunction associated with normal, decreased, or increased
platelet counts (Figs. 2,3,4).
A thorough medical, family, and drug history is essential in establishing
the etiology of platelet dysfunction, as is exclusion of coagulation
and fibrinolytic disorders.
In all of the disorders discussed below, the results of the coagulation
screening tests PT and APTT should be considered normal.
Platelet dysfunction with normal platelet count
Platelet dysfunction with a normal platelet count usually indicates
a qualitative platelet disorder. In following the algorithm in Fig.
2, these disorders would be evaluated in a patient with a normal
PT, APTT, and platelet count. An initial platelet function test,
such as the PFA-100 or a bleeding time, would be abnormal, and tests
for von Willebrand disease would be normal. Platelet aggregation
studies would then be used to test for Glanzmann thrombasthenia,
Bernard-Soulier disease, and platelet storage pool disorders. This
would be followed by more specific tests, if required.
Drug-induced platelet dysfunction is probably the most common
cause of platelet-mediated bleeding and will also demonstrate platelet
dysfunction with a normal platelet count, so it is extremely important
to take a careful drug history.5
A list of drugs that cause platelet dysfunction can be found in
Table 1. Platelet aggregation
abnormalities typically found with drugs such as aspirin, GP IIb/IIIa
antagonists, or the thienopyridines can be found in Table
Glanzmann thrombasthenia is a congenital deficiency or dysfunction
of GP IIb/IIIa, the receptor for fibrinogen, and is responsible
for mediating platelet aggregation.11
It is an autosomal recessive disorder that manifests in lifelong
mucocutaneous bleeding. Mutations of GP IIb and GP IIIa have been
implicated.12 The initial platelet
function test will be abnormal in patients with Glanzmann thrombasthenia.
No aggregation response will result from adding ADP, collagen, epinephrine,
and arachidonic acid-aggregating agents, whereas the ristocetin-induced
aggregation is normal11 (Table
2). This finding is virtually diagnostic of Glanzmann thrombasthenia,
but the disorder can be confirmed by platelet flow cytometry or
crossed immunoelectrophoresis of platelet membrane proteins.
Abnormalities of platelet secretion can be due to deficiency of
platelet granules or defects in the signal transduction events that
regulate secretion or aggregation.13
Platelet storage pool disorders can be congenital or acquired and
result from a deficiency of granules (alpha or dense granules, or
both) or a defective release of granules at platelet activation.14
Dense granule storage pool disorders (δ-SPDs) can appear as
a singular clinical entity or as part of other hereditary disorders,
such as Chediak-Higashi, Hermansky-Pudlak syndrome, thrombocytopenia
with absent radii (TAR syndrome), or Wiskott-Aldrich syndrome.14
δ-SPD often shows decreased aggregation response to ADP, epinephrine,
and collagen and normal aggregation to arachidonic acid and ristocetin
(Table 2). Decreased ATP
release by lumiaggregometry and decreased mepacrine uptake/release
by flow cytometry are observed. Ultrastructural abnormalities in
these disorders usually show decreased dense granules. Furthermore,
α-SPD (gray platelet syndrome) has decreased alpha granules
and is usually considered a macrothrombocytopenia (see the subheading
Platelet disorders with thrombocytopenia).15
A rare α/δ-SPD that has features of both disorders has
been described in the literature. Acquired platelet storage pool
disorders can be seen with underlying myeloproliferative disorders
or in clinical scenarios where there is ongoing in vivo platelet
activation, such as cardiopulmonary bypass, disseminated intravascular
coagulation, and thrombotic thrombocytopenic purpura/hemolytic uremic
In addition to being seen in storage pool disorders, platelet
release defects can be found with defects of platelet signal transduction.
These generally are a poorly defined group of disorders, but they
may constitute a significant percentage of patients with abnormal
secondary wave of aggregation and decreased granule release in whom
alpha and dense granules are not deficient.13
Other significant disorders of platelet function that have platelet
counts in the normal range usually are acquired with the presence
of another disease or drug therapy.5
These are far more common than the aforementioned disorders. Platelet
dysfunction is often observed with chronic renal failure or liver
disease in patients suffering from a variety of myeloproliferative
and lymphoproliferative disorders-for example, polycythemia vera,
myelofibrosis, paroxysmal nocturnal hemoglobinuria, acute myelogenous
leukemia, and hairy cell leukemia.
Platelet dysfunction also may be associated with a variety of
clinical scenarios, such as previous cardiopulmonary bypass, implantation
of prosthetic materials, including vascular grafts and prosthetic
heart valves, and use of ventricular assistance devices. Platelet
dysfunction in these disorders usually is difficult to characterize
because nonspecific defects of platelet aggregation typically are
Platelet disorders with thrombocytosis
Patients with elevated platelet counts may have clinical bleeding,
but they may also be asymptomatic or have thrombosis. In these patients,
laboratory evaluation should focus on elucidating the cause of the
thrombocytosis, and it should include a complete blood cell count,
peripheral blood smear, bone marrow evaluation, cytogenetic study,
and platelet aggregation study. Platelet function screening tests,
in general, have little utility in evaluating these disorders and
do not necessarily correlate with additional platelet function tests.
In patients with thrombocytosis, the differential diagnosis is
primarily between a reactive thrombocytosis and a myeloproliferative
process (essential thrombocytosis, chronic myelogenous leukemia,
polycythemia vera, and myelofibrosis). The algorithmic approach
to the diagnosis of thrombocytosis is shown in Fig.
2. Patients with a myeloproliferative disorder typically have
platelet counts greater than 1 x 106/µL,
and patients with reactive thrombocytoses have lower counts, but
there is a great deal of overlap. For myeloproliferative disorders,
characteristic features of a specific disease can be discerned by
examining the peripheral blood smear and bone marrow and with cytogenetic
Platelet aggregation studies alone can suggest an underlying myeloproliferative
disorder, particularly when epinephrine-induced aggregation alone
is reduced or absent.16 The decreased
epinephrine-induced aggregation is thought to be due to down-regulation
of α2-adrenergic receptors.
Other patterns of platelet dysfunction with myeloproliferative
disorders include decreased platelet aggregation to ADP or collagen,
dense-granule storage pool pattern, abnormal platelet morphology,
abnormalities of the arachidonic acid pathway, decreased receptors
for prostaglandin D2, or increased aggregation with various agonists.
In the clinical evaluation of patients with myeloproliferative disorders,
it is important to remember that bleeding and thrombosis can be
observed in these patients and that the results of the platelet
function tests will not necessarily distinguish whether a patient
is at risk for bleeding or thrombosis.
In contrast to patients with myeloproliferative disorders, patients
with reactive thrombocytosis usually have normal platelet function.
A reactive, or secondary, thrombocytosis can be associated with
many clinical entities, including iron deficiency, inflammatory
and infectious disorders post-splenectomy in such malignancies as
carcinomas or lymphomas, as well as myelodysplastic disorders, smoking,
and exercise. It can also be observed as a rebound thrombocytosis
following splenectomy, treatment for idiopathic thrombocytopenic
purpura, pernicious anemia, or after cessation of myelosuppressive
Platelet disorders with thrombocytopenia
Disorders in which the platelet count is decreased can be divided,
for evaluation purposes, by the size of the platelets. Thrombocytopenias
can be congenital or acquired, but they have been grouped by platelet
size in this discussion. (See Fig.
3 for an algorithmic approach to small and large platelets and
Fig. 4 for an approach to
the diagnosis of normal-sized platelets.) Initial evaluation of
the platelet count must take into consideration any spurious or
pseudothrombocytopenia. Pseudothrombocytopenia is often due to cold-reacting
platelet agglutinins or platelet binding to neutrophils (platelet
satellitism). The agglutinins are often seen in patients with high
immunoglobulin levels or infections and usually bind platelets only
when calcium is chelated, such as in an EDTA blood collection tube.
Pseudothrombocytopenia can be diagnosed by examining a peripheral
smear where large aggregates of platelets are observed, often around
the feathered edge. A more accurate platelet count can be established
by collecting the blood sample in citrate or heparin anticoagulants.
Thrombocytopenia with small platelets can be seen in patients
with Wiskott-Aldrich syndrome.17
This is an X-linked recessive disorder characterized by immunologic
abnormalities, recurrent infections, eczema, and thrombocytopenia.
The mean platelet volume, a measure of platelet size included in
most CBCs, is often low (about half normal size). Platelet dysfunction
is severe; the platelets are unable to aggregate and a storage pool-like
pattern is often seen. Patients with thrombocytopenia due to marrow
aplasia may also have small platelets, but the MPV is usually low-normal,
The rare macrothrombocytopenia disorders are congenital in nature
and most are inherited in an autosomal dominant fashion. They usually
are due to congenital defects in platelet production by megakaryocyte
or demarcation membrane systems, although the structural or genetic
abnormalities are known in only a few disorders18
(Fig. 3). Some patients
with acquired platelet destruction and turnover, such as idiopathic
thrombocytopenic purpura, may have high MPVs due to the rapid release
of new platelets, but the macrothrombocytopenia syndrome platelets
generally are much larger and more uniform in size.
Bernard-Soulier disease, the most well-characterized of the macrothrombocytopenia
disorders, is a congenital deficiency of the platelet glycoprotein
Ibα/Ibβ/IX/V receptor, the surface receptor for VWF-mediated
platelet aggregation.19 Many patients
with Bernard-Soulier disease have severe bleeding with moderately
severe thrombocytopenia and large platelets. Most of the Bernard-Soulier
genetic defects are due to mutations of the GPIbα gene, but
they may also be due to defects of the GP Ibβ or GP IX genes.
Normal platelet aggregation is noted with exposure to ADP, collagen,
epinephrine, and arachidonic acid, but aggregation is absent when
ristocetin is added ( ).
The glycoprotein abnormality can be confirmed with flow cytometry
or crossed immunoelectrophoresis. Additional laboratory studies
show normal VWF antigen and ristocetin cofactor activity distinguish
Bernard-Soulier syndrome from von Willebrand disease.
Patients who are heterozygous for the disease will show only giant
platelets on a blood smear without hypoplatelet function, thrombocytopenia,
or bleeding. These heterozygous patients may have associated velopharyngeal
insufficiency, conotruncal heart disease, and learning disabilities
and are classified as having the velocardiofacial syndrome.
Gray platelet syndrome is an autosomal dominant α-SPD characterized
by mild bleeding symptoms, reticulin fibrosis of the bone marrow,
variable thrombocytopenia, and large (mean, 13 fL) platelets that
appear gray on the peripheral blood smear due to decreased alpha
granules.15 Pale platelets can
also be seen with ongoing platelet activation and circulating "exhausted"
platelets, but these patients will have a mixture of normal and
pale platelets. Other rare macrothrombocytopenias are listed in
Several macrothrombocytopenia disorders are characterized by neutrophilic
inclusions. May-Hegglin anomaly is the most common macrothrombocytopenia.
It is an autosomal dominant disorder characterized by Dohle body
inclusions in neutrophils with a mild bleeding disorder.18
A peripheral smear shows a modest thrombocytopenia with uniformly
large platelets. Laboratory studies will usually show normal platelet
aggregation and a normal bleeding time, attesting to the increased
functionality of the larger platelets. Electron microscopic analysis
of platelets in May-Hegglin anomaly will often show disorganized
microtubles. Electron microscopic analysis of the neutrophilic inclusions
shows them to lack a limiting membrane, to be free of specific granules,
and to contain parallel bundles of ribosomes, microfilaments, and
segments of endoplasmic reticulum.
The two other macrothrombocytopenia disorders with neutrophilic
inclusions are Fechtner syndrome and Sebastian syndrome. Fechtner
syndrome can be distinguished by hereditary nephritis, deafness,
cataracts (Alport syndrome), and macrothrombocytopenia. Sebastian
syndrome, on the other hand, has no specific clinical associations.
In thrombocytopenic platelet disorders with normal platelet morphology
and size, marrow examination may be helpful in differentiating the
underlying causes. This group of disorders includes congenital and
acquired thrombocytopenias that usually are due to decreased platelet
production or increased platelet destruction (Fig.
4). The number of megakaryocytes on the bone marrow can help
distinguish between these etiologies, but analysis of platelet turnover
by mRNA analysis (analogous to a platelet reticulocyte count) may
also be helpful.
The finding of adequate or increased megakaryocytes on the bone
marrow or increased reticulated platelets suggests peripheral platelet
destruction. Platelet function tests typically do not help in differentiating
between the entities in this class of disorders because most function
studies will give abnormal results simply due to the low platelet
number. The overall MPV is usually normal with destructive thrombocytopenia,
but platelet sizes typically vary, and many large platelets are
seen, indicating rapid platelet turnover. These disorders are invariably
acquired, and an underlying abnormality should be sought. The clinical
scenario generally is the most helpful in classifying these disorders.
Idiopathic thrombocytopenic purpura is known to be due to platelet
sensitization, with autoantibodies leading to platelet destruction
in the reticuloendothelial system. Peripheral smears may show variable
macrothrombocytopenia, and autoantibodies to specific surface glycoproteins
can be detected by flow cytometry or immunoassay,20
although diagnosis is largely from clinical findings. Other immune
thrombocytopenias include post-transfusion purpura and neonatal
alloimmune thrombocytopenia, which often occur because of polymorphisms
of platelet antigens, such as PLA1
The thrombocytopenia of thrombotic thrombocytopenic purpura is
thought to be secondary to deficiency of a VWF-cleaving metalloproteinase
in many patients, leading to diffuse thrombus formation in small
vessels and a decline in circulating platelets.22
These patients will show characteristic clinical symptoms, such
as renal failure, mental status changes, fever, and hemolysis with
prominent schistocytes on the peripheral blood smear but normal
screening coagulation studies. An assay for the VWF-cleaving metalloproteinase
has been developed, but because it is based on the VWF multimer
assay, it is not readily available in most laboratories.
Drug-induced thrombocytopenias attributed to immunologic platelet
destruction can be seen with many drugs, but the most common offenders
are quinidine, quinine, heparin, sulfonamide drugs, and gold salts.
Drug-induced thrombocytopenias can be diagnosed by detecting platelet-associated
antibody by flow cytometry, although this is a nonspecific finding
that can also be seen with infections and autoimmune disorders.
The drug dependence of the antibody binding can be demonstrated
by incubating platelets with patient plasma in the presence of the
Heparin-induced thrombocytopenia is a distinctive drug-induced
thrombocytopenia associated with heparin therapy in which antibodies
are formed to heparin-platelet factor 4 complexes, leading to platelet
aggregation, platelet microparticle formation, endothelial injury,
and paradoxical thrombosis.23
The thrombocytopenia is often delayed five to 12 days after starting
heparin therapy and usually resolves after heparin therapy is stopped.
Specific laboratory tests, such as heparin-induced platelet aggregation,
serotonin release, and heparin-platelet factor 4 enzyme-linked immunosorbent
assay, are available to diagnose this disorder.
Platelet-derived bleeding diatheses have multiple causes. Laboratory
evaluation of these disorders can range from simple to complex but
should initially include an extensive evaluation of the patient's
medical history, concentrating on personal and familial bleeding
disorders and medications being taken. Using this information and
the aforementioned algorithms may help clinicians or pathologists
determine the underlying origin for platelet-derived bleeding.n
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Dr. Corcoran is a pathology of laboratory medicine resident,
Cleveland (Ohio) Clinic Foundation. Dr. Kottke-Marchant is section
head of hemostasis and thrombosis in the Department of Clinical
Pathology, Cleveland Clinic Foundation. She is also a member of
the CAP Coagulation Resource Committee.